A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors

Osteoporosis Clinical Trial

Official title:

Diminished Bone Mineral Density in Survivors of Childhood Acute Lymphoblastic Leukemia (ALL): A Severity-Adapted Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00186901
• Other study ID #: BONEII
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: December 6, 2012
• Start date: July 2000
• Est. completion date: September 2011

Study information

• Verified date: December 2011
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Research studies have shown that children who are long-term survivors of childhood leukemia may be at greater risk for early bone loss called osteoporosis. This bone loss may lead to a greater risk of broken bones and other spine and bone problems. However, researchers still do not know much about how frequently this long-term side effect may occur and how severe the problem is.

St. Jude Children's Research Hospital researchers want to determine the frequency and severity of this side effect. They are also studying whether taking calcium and Vitamin D supplements can help children at risk for osteoporosis and if certain factors can be identified -- such as age at diagnosis, cancer treatments, or family history -- that may increase the chances of having osteoporosis. Researchers will take an x-ray study called quantitative computed tomography (QCT) to measure bone mineral density (BMD). The BMD is a measure of bone strength. If a subject's BMD falls below the average, he/she will be assigned to one of two groups. Subjects will be randomly assigned (like tossing a coin) to receive calcium and vitamin D pills. The other half will receive placebo pills that look like the calcium and vitamin D pills.

Description:

The main objectives of the study are:

• To estimate, using quantitative computed tomography (QCT), the prevalence of diminished bone mineral density (BMD) in patients treated with contemporary, protocol-based multiagent chemotherapy (+cranial irradiation) for childhood acute lymphoblastic leukemia (ALL).

• To investigate possible risk factors for the development of diminished BMD in patients treated with contemporary protocol-based therapy for childhood ALL. Factors to be examined include patient characteristics (age at the time of treatment, gender, race, body mass index, physical activity and nutritional status, menarchal status, oral contraceptive use, growth hormone therapy, smoking and alcohol intake, birth weight, fracture history); treatment effects (intensity of treatment with antimetabolites and glucocorticoids; history of cranial irradiation); and genetic predisposition (i.e., vitamin D and CYP3A4 receptor polymorphism and family history of osteoporosis).

• To evaluate, in a prospective placebo-controlled double-blinded randomized trial, the effects of vitamin D and calcium supplementation in addition to nutritional counseling on BMD in patients with BMD scores below the mean for age- and gender-matched controls, compared to an educational program of nutritional counseling alone.

Secondary Aim

• To evaluate, in a prospective randomized trial, the correlation between BMD as determined by QCT and BMD as determined by dual energy x-ray absorptiometry (DEXA) in patients with BMD more than one standard deviation (SD) below the mean for age- and gender-matched controls.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 429
• Est. completion date: September 2011
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patient is a survivor of acute lymphoblastic leukemia.

• Patient was treated on St. Jude Children's Research Hospital's Total XI, XII, or XIII treatment protocol.

• Patient is at least five years out from completion of therapy and is in first remission

Exclusion Criteria:

• Active disease

• Pregnant or lactating females

• Inability to chew and swallow pills

• Currently taking more than 800 mg supplemental calcium or 800 IU vitamin D

• Anemia

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoblastic, Acute
• Leukemia, Lymphoid
• Osteoporosis
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Calcium carbonate (Tums), vitamin D
Calcium carbonate 100mg/day (Tums), vitamin D 800 units/day

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Metabolic Bone Center at the University of Tennessee	Memphis	Tennessee
United States	Preventive Medicine, University of Tennessee	Memphis	Tennessee
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

References & Publications (2)

Crom DB, Tyc VL, Rai SN, Deng X, Hudson MM, Booth A, Rodrigues LN, Zhang L, McCammon E, Kaste SC. Retention of survivors of acute lymphoblastic leukemia in a longitudinal study of bone mineral density. J Child Health Care. 2006 Dec;10(4):337-50. — View Citation

Kaste SC, Rai SN, Fleming K, McCammon EA, Tylavsky FA, Danish RK, Rose SR, Sitter CD, Pui CH, Hudson MM. Changes in bone mineral density in survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2006 Jan;46(1):77-87. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD)	The effect of taking calcium and vitamin D supplements was measured using Quantitative Computed Tomography (QCT) to calculate a QTC Z score. A standardized Z-score was calculated to indicate the difference between the patient's Bone Mineral Density (BMD) and the mean value for age and gender-appropriate controls. Z-scores from 0 to +2 are considered normal, above +2 are considered to be elevated, from 0 to -1 are considered to represent a mild BMD deficit, between -1 and -2 are considered to represent moderate deficits, and below -2 are considered to represent severe deficits.	Baseline	No
Primary	Bone Mineral Density in Male and Female ALL Survivors	Using bone mineral density Z-score, assess relationship between predisposing factors (gender) and bone mineral density; a negative value indicates a deficit in bone mineral density.	Baseline	No
Primary	Bone Mineral Density by Race of ALL Survivors	Using bone mineral density Z-score, assess relationship between predisposing factors (race) and bone mineral density; a negative value indicates a deficit in bone mineral density.	Baseline	No
Primary	Bone Mineral Density by Age Group of ALL Survivors	Using bone mineral density Z-score, assess relationship between predisposing factors (age groups) and bone mineral density; a negative value indicates a deficit in bone mineral density.	Baseline	No
Secondary	Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.	To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 121 patients at baseline were assessed by both method the QCT and DXA methods to assess Bone Mineral Density.	Baseline	No
Secondary	Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.	To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 218 patients were assessed at 12 months for QCT. 94 were evaluated using DXA. 94 patients received both scans.	12 months	No
Secondary	Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.	To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 188 patients were assessed at 24 months by the QCT method and 90 were evaluated using the DXA methods to assess Bone Mineral Density. 90 patients received both scans.	24 months	No
Secondary	Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.	To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 180 patients were assessed at 36 months by the QCT method and 89 were evaluated using the DXA methods to assess Bone Mineral Density. 89 patients received both scans.	36 months	No
Secondary	To Investigate Possible Risk Factors (Apa1 Vitamin D Receptor) for the Development of Diminished BMD in Patients Treated With Contemporary Protocol-based Therapy for Childhood ALL	The Apa1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood	At enrollment	No
Secondary	To Investigate Possible Risk Factors (Bsm1 Vitamin D Receptor) for the Development of Diminished BMD in Patients Treated With Contemporary Protocol-based Therapy for Childhood ALL	The Bsm1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood	At enrollment	No

External Links

•   St. Jude Children's Research Hospital